Host-­pathogen interfaces are locked in a genetic conflict that drives their rapid evolution. In this work, we evaluate the evolutionary potential of rapidly evolving residues at antiviral interfaces in the broadly-­acting antiviral protein MxA GTPase. We employ a mutagenesis approach to assay novel MxA variants and test their antiviral functionality against the orthomyxoviruses thogotovirus and influenza A virus. Through this method, we have uncovered intrinsic properties of amino acid interactions at antiviral interfaces and generated novel MxA variants with enhanced antiviral activity.

Discrimination of self from non-self through the continuous selection of effector specificity is the backbone of effective
immunity. For natural killer (NK) cells this specificity is achieved by unique combinations of variable germ-line receptors that
recognize self-MHC antigens. Inhibitory interaction between NK cell receptors and self-ligands is the key determinant in
functional potentiation of pre-primed effector responses, a process termed NK cell education. The calibration of effector
potential to self-MHC allows for the rapid sensing of discontinuity in the level of MHC expression during infection, cellular
stress or tumor transformation, whilst operating within a framework of overall tolerance to normal tissues. While NK cell
tolerance is firmly established across species the underlying mechanism that connects the inhibitory signal to the
development of intrinsic functional potential has yet to be resolved. We describe here the first stable imprint of NK cell
education, the granular accumulation of granzyme B that occurs specifically in NK cells under inhibitory self-interaction.
This accumulation underlies the development of natural killer cell potential, traced first in the regulatory shift from inducible
to constitutive effector transcription that occurs during NK cell differentiation, then shaped by surface signaling through killer
cell immunoglobulin-like receptors, as maturing NK cells continuously interact with their environment.

Contact : thierry.walzer@inserm.fr

Amphi Pasteur CERVI

vendredi
13 / 01 / 2017
11h00

« Cis- and trans-acting regulations of mRNA biogenesis and their impact on genetic stability »

Benoît PALANCADE

Invité par V. Vanoosthuyse

Salle des Thèses Chantal Rabourdin-Combe

Jeudi
19 / 01 / 2017
11h00

« C.elegans in an evolutionary and ecological context »

Marie-Anne FELIX (IBENS, Paris)

Salle des Thèses Chantal Rabourdin-Combe

Lundi
23 / 01 / 2017
11h00

“Cell division licensing in Vibrio cholerae, a bacterium with a divided genome”

Cell division must be coordinated with chromosome replication and segregation to ensure the faithful transmission of genetic information during proliferation. In most bacteria, assembly of the division apparatus, the divisome, starts with the polymerization of a tubulin homologue, FtsZ, into a ring-like structure at mid-cell, the Z-ring. It typically occurs at half of the cell cycle when most of the replication and segregation cycle of the unique chromosome they generally harbour is achieved. The chromosome itself participates in the regulation of cell division, at least in part because it serves as a scaffold to position FtsZ polymerization antagonists. However, about 10% of bacteria have more than one chromosome, which raises questions about the way they license cell division. For instance, the genome of Vibrio cholerae, the agent of cholera, is divided between a 3 Mbp replicon that originates from the chromosome of its mono-chromosomal ancestor, Chr1, and a 1 Mbp plasmid-derived replicon, Chr2. Here, we show that Chr2 harbours binding motifs for an inhibitor of Z-ring formation, which helps accurately position the V. cholerae divisome at mid-cell and postpones its assembly to the very end of the cell cycle.